The indirect assessment of tissue flow by hemodynamic method is useful, but does not reflect varying degrees of ischemia, and there is no consensus as to what are critical pressure levels. By percutaneous biopsies muscle samples can be obtained and changes in high energy phosphate compounds measured, allowing direct correlation with the widely used hemodynamic studies. In mongrel dogs graded ischemia will be induced, and distal limb blood pressure and flow measured, and correlated with changes in muscle energy metabolism, and alterations in transmembrane cell potential. Clinical studies of patients with ischemic extremities will be performed in a similar fashion; segmental limb pressures at rest and with exercise will be correlated with changes in muscle metabolism. In patients undergoing amputation, alterations in muscle cellular energetics, transmembrane cell potential, and segmental limb pressures will be compared proximal and distal to the amputation site. These direct techniques for evaluating cellular energetics offer a precise method for determining critical levels of blood pressure and flow.